Increased expression of interleukin-6 gene in gastritis and gastric cancer

Helicobacter pylori (H. pylori) induces an intense inflammatory response, mediated by proinflammatory cytokines, including interleukin (IL)-6 and its membrane receptor (IL-6R), which activates important signaling pathways in the development of gastric disease and cancer. We investigated the gene and protein expression of IL-6 and IL-6R and the influence of polymorphisms rs1800795, rs1800796, and rs1800797 on its gene expression together with H. pylori infection. Furthermore, an in-silico analysis was performed to support our results. Gastric biopsies were obtained from patients with gastric symptoms and patients with gastric cancer (GC) and were divided into groups (Control, Gastritis, and Cancer). H. pylori was detected by PCR. Real-time-qPCR was employed to determine gene expression, and western blot assay was used to analyze protein expression levels. PCR-RFLP was used to characterize IL-6 polymorphisms. Bioinformatics analyses were performed using the Gene Expression Omnibus (GEO) database and GEO2R to screen out differentially expressed genes (DEGs). H. pylori was detected in 43.3% of the samples. Statistically significant differences were found for IL-6 (P=0.0001) and IL-6R (P=0.0005) genes among the three groups, regardless of the presence of H. pylori. Among patients with H. pylori infection, the IL-6 and IL-6R gene and protein expressions were significantly increased, highlighting IL-6 gene overexpression in patients with GC. No statistically significant differences were found for the rs1800795, rs1800796, and rs1800797 polymorphisms compared to IL-6 gene expression. The results indicated that the IL-6 polymorphisms do not influence its expression, but IL-6 and IL-6R expression seems to be altered by the presence of H. pylori.

幽门螺杆菌（Helicobacter pylori，H. pylori）可诱发强烈的炎症反应，该反应由包括白细胞介素-6（interleukin，IL-6）及其膜受体IL-6R在内的促炎细胞因子所介导，上述因子可激活胃部疾病及胃癌发生发展中的关键信号通路。本研究针对IL-6与IL-6R的基因及蛋白表达情况，以及rs1800795、rs1800796、rs1800797三个基因多态性位点对IL-6基因表达的影响，联合幽门螺杆菌感染状态展开了探究。
此外，本研究还开展了计算机辅助分析（in silico analysis）以佐证实验结果。
本研究从伴有胃部症状的患者及胃癌（gastric cancer，GC）患者体内采集胃活检组织，并将其分为三组：对照组（Control）、胃炎组（Gastritis）与癌症组（Cancer）。采用聚合酶链反应（polymerase chain reaction，PCR）检测样本中的幽门螺杆菌感染情况；通过实时定量聚合酶链反应（Real-time-qPCR）测定基因表达水平；利用蛋白质免疫印迹实验（western blot assay）分析蛋白表达量；采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）对IL-6基因多态性进行分型。
本研究依托基因表达综合数据库（Gene Expression Omnibus，GEO）及GEO2R工具开展生物信息学分析，以筛选差异表达基因（differentially expressed genes，DEGs）。
结果显示，43.3%的样本检测出幽门螺杆菌感染。三组样本的IL-6（P=0.0001）与IL-6R（P=0.0005）基因表达水平均存在显著统计学差异，且该差异不受幽门螺杆菌感染状态的影响。
在幽门螺杆菌感染阳性患者中，IL-6及IL-6R的基因与蛋白表达水平均显著升高，其中胃癌患者的IL-6基因过表达现象尤为突出。
相较于IL-6基因表达，rs1800795、rs1800796及rs1800797三个多态性位点未呈现显著统计学差异。
本研究结果表明，IL-6基因多态性不会对其自身表达产生影响，但幽门螺杆菌的存在可显著改变IL-6与IL-6R的表达水平。